tbuckley/cabot-search huggingface dataset:
Quantitative insights into effects of intrapartum antibiotics and birth mode on infant gut microbiota in relation to well-being during the first year of life
Authors: Roosa Jokela, Katri Korpela, Ching Jian, Evgenia Dikareva, Anne Nikkonen, Terhi Saisto, Kirsi Skogberg, Willem M. de Vos, Kaija-Leena Kolho, Anne Salonen
Journal: Gut Microbes (2022)

Birth mode and maternal intrapartum (IP) antibiotics affect infants' gut microbiota development, but their relative contribution to absolute bacterial abundances and infant health has not been studied. We compared the effects of Cesarean section (CS) delivery and IP antibiotics on infant gut microbiota development and well-being over the first year. We focused on 92 healthy infants born between gestational weeks 37–42 vaginally without antibiotics (N = 26), with IP penicillin (N = 13) or cephalosporin (N = 7) or by CS with IP cephalosporin (N = 33) or other antibiotics (N = 13). Composition and temporal development analysis of the gut microbiota concentrated on 5 time points during the first year of life using 16S rRNA gene amplicon sequencing, integrated with qPCR to obtain absolute abundance estimates. A mediation analysis was carried out to identify taxa linked to gastrointestinal function and discomfort (crying, defecation frequency, and signs of gastrointestinal symptoms), and birth interventions. Based on absolute abundance estimates, the depletion of Bacteroides spp. was found specifically in CS birth, while decreased bifidobacteria and increased Bacilli were common in CS birth and exposure to IP antibiotics in vaginal delivery. The abundances of numerous taxa differed between the birth modes among cephalosporin-exposed infants. Penicillin had a milder impact on the infant gut microbiota than cephalosporin. CS birth and maternal IP antibiotics had both specific and overlapping effects on infants' gut microbiota development. The resulting deviations in the gut microbiota are associated with increased defecation rate, flatulence, perceived stomach pain, and intensity of crying in infancy.
Controversy Over "Patterning" as a Treatment for Brain Damage in Children
Authors: Roger D. Freeman
Journal: JAMA (1967)

Treatment methods for brain damage devised by the Institutes for the Achievement of Human Potential in Philadelphia have received much publicity and have been introduced in parts of the United States and several foreign countries. Controversy continues as to the validity of the claimed results, the reasons for resistance to the acceptance of these claims, and the effects of other activities of the institutes, such as their advocacy of early teaching of reading. The validity of the objections and the claimed results cannot be established at present. It is concluded, however, that a major source of negative professional feeling has been the inappropriate publicity given to claims of results which have not been documented or supported in a scientific manner.
An Attitudinal Assessment of Faculty Practice Plans
Authors: Gordon K. MacLeod
Journal: JAMA (1987)

An awareness of potential conflict between medical schools and private practice prompted an attitudinal assessment of faculty practice plans (FPPs). A representative sample of eight medical school FPPs in seven different communities was selected for study. For each FPP, a sample of health care leaders, stratified at different levels of administrative responsibility, was selected from academic medical centers and from community settings. Topics for FPP assessment were chosen for their relevance to physician and lay administrators involved with academic and community practice. Questions were answered on a yes-no basis and were graded by intensity of response. Although only two of the questions revealed statistical disparity on a simple yes-no basis, the intensity of response differed significantly in eight of the 14 questions asked. This study gives consideration to the strategic implications of FPPs for universities, medical schools, and organized medicine. (<i>JAMA</i>1987;257:1072-1075)
Highlights of This Issue
Journal: Clinical Cancer Research (2015)

It is becoming evident that, among HER2-positive breast tumors, the expression of HER2 is variable. Scaltriti and colleagues investigated the correlation between levels of both HER2 and the truncated isoform p95HER2 in the primary tumors and likelihood to achieve clinical response by anti-HER2 therapy. The authors found that p95HER2 and HER2 expression correlated and that high levels of these receptors predicted for complete tumor remission (and progression-free survival) in response to the combination of trastuzumab and lapatinib. This study proposes HER2 quantification as a tool to identify those patients that are more likely to benefit from dual HER2 therapy.Predictive biomarkers to epidermal growth factor receptor (EGFR) inhibitors in recurrent and/or metastatic squamous cell carcinoma of head and neck (R/M-SCCHN) have been elusive. Kim and colleagues conducted a phase II biomarker trial of dacomitinib, an oral irreversible pan-HER tyrosine kinase inhibitor, in R/M-SCCHN using next-generation sequencing and digital count technology. Dacomitinib showed significantly higher antitumor activity in R/M-SCCHN patients without PI3K-pathway alteration or inflammatory cytokine expression. Screening for phosphoinositide 3-kinase (PI3K)-pathway alteration and/or inflammatory gene expression could help identify subgroups most likely benefit from dacomitinib in R/M-SCCHN.Medulloblastoma, a common malignant brain tumor in pediatric and adult patients, has recently been redefined by the molecular pathways that drive tumorgenesis. Sonic hedgehog (SHH) activation has been recognized as a common pathway mutated in these tumors. Shou and colleagues describe the development of a five-gene assay that preselects patients with SHH activated medulloblastoma. Validation of this signature was confirmed in independent data sets with 100% concordance using gene expression profiling. Sonidegib, a SHH inhibitor that targets the upstream mutation in this pathway, including hedgehog, patch and smoothen, which account for approximately 70% of the mutations in this pathway, was evaluated in a prospective clinical trial in adult and pediatric medulloblastoma patients. The five-gene assay accurately predicted 6 of 9 responses and 41/41 nonresponders. This test accurately preselects patients that may respond to this targeted therapy, while allowing those without the target to avoid therapy that would not provide any benefit.O'Brien and colleagues have analysed serum markers CA19-9, CA125, CEACAM1, and REG3A in samples taken years in advance of the clinical presentation of pancreatic cancer. CA19-9 and CA125 were elevated many months prior to diagnosis and in combination improved the performance of CA19-9 alone, with lead times of 20-23 months for test-positive cases. CEACAM1 and REG3A were late markers adding little in combined models. This work challenges the prevailing view that CA19-9 is upregulated late in the course of pancreatic cancer development and suggests its potential for screening high-risk groups, particularly if used longitudinally.
A Wow for Neoadjuvant ICI in dMMR Colon Cancer
Journal: Cancer Discovery (2022)

Data from the NICHE-2 study indicate that patients with operable mismatch repair-deficient colon cancer benefit considerably from neoadjuvant immune checkpoint inhibition. A brief period of treatment with nivolumab and ipilimumab induced high pathologic response rates, did not delay surgery, and checked disease recurrence for a median of 13.1 months so far.
DNA methylation profile in CpG-depleted regions uncovers a high-risk subtype of early-stage colorectal cancer
Authors: Huichuan Yu, Xiaolin Wang, Liangliang Bai, Guannan Tang, Kelly T Carter, Ji Cui, Pinzhu Huang, Li Liang, Yanqing Ding, Muyan Cai, Meijin Huang, Huanliang Liu, Guangwen Cao, Steven Gallinger, Rish K Pai, Daniel D Buchanan, Aung Ko Win, Polly A Newcomb, Jianping Wang, William M Grady, Yanxin Luo
Journal: JNCI Journal of the National Cancer Institute (2022)

Abstract Background The current risk stratification system defined by clinicopathological features does not identify the risk of recurrence in early-stage (stage I-II) colorectal cancer (CRC) with sufficient accuracy. We aimed to investigate whether DNA methylation could serve as a novel biomarker for predicting prognosis in early-stage CRC patients. Methods We analyzed the genome-wide methylation status of CpG loci using Infinium MethylationEPIC array run on primary tumor tissues and normal mucosa of early-stage CRC patients to identify potential methylation markers for prognosis. The machine-learning approach was applied to construct a DNA methylation–based prognostic classifier for early-stage CRC (MePEC) using the 4 gene methylation markers FAT3, KAZN, TLE4, and DUSP3. The prognostic value of the classifier was evaluated in 2 independent cohorts (n = 438 and 359, respectively). Results The comprehensive analysis identified an epigenetic subtype with high risk of recurrence based on a group of CpG loci in the CpG-depleted region. In multivariable analysis, the MePEC classifier was independently and statistically significantly associated with time to recurrence in validation cohort 1 (hazard ratio = 2.35, 95% confidence interval = 1.47 to 3.76, P &amp;lt; .001) and cohort 2 (hazard ratio = 3.20, 95% confidence interval = 1.92 to 5.33, P &amp;lt; .001). All results were further confirmed after each cohort was stratified by clinicopathological variables and molecular subtypes. Conclusions We demonstrated the prognostic statistical significance of a DNA methylation profile in the CpG-depleted region, which may serve as a valuable source for tumor biomarkers. MePEC could identify an epigenetic subtype with high risk of recurrence and improve the prognostic accuracy of current clinical variables in early-stage CRC.
Quantifying Clinical Utility of Adjuvant Abemaciclib in Patients With High-risk Early Breast Cancer Who Received Neoadjuvant Chemotherapy
Authors: Ryan Sun, Lee-Jen Wei
Journal: JAMA Oncology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Cancer risks by sex and variant type in PTEN hamartoma tumor syndrome
Authors: Linda A J Hendricks, Nicoline Hoogerbrugge, Arjen R Mensenkamp, Joan Brunet, Roser Lleuger-Pujol, Hildegunn Høberg-Vetti, Marianne Tveit Haavind, Giovanni Innella, Daniela Turchetti, Stefan Aretz, Isabel Spier, Marc Tischkowitz, Arne Jahn, Thera P Links, Maran J W Olderode-Berends, Ana Blatnik, Edward M Leter, D Gareth Evans, Emma R Woodward, Verena Steinke-Lange, Violetta C Anastasiadou, Chrystelle Colas, Marie-Charlotte Villy, Patrick R Benusiglio, Anna Gerasimenko, Valeria Barili, Maud Branchaud, Claude Houdayer, Bianca Tesi, M Omer Yazicioglu, Rachel S van der Post, Janneke H M Schuurs-Hoeijmakers, Liselotte P van Hest, Muriel A Adank, Floor Duijkers, Maartje Nielsen, Katja C J Verbeek, Yvette van Ierland, Jacques C Giltay, Janet R Vos, Janet R Vos
Journal: JNCI Journal of the National Cancer Institute (2022)

PTEN Hamartoma Tumor Syndrome (PHTS) is a rare syndrome with a broad phenotypic spectrum, including increased risks of breast (BC, 67%-78% at age 60 years), endometrial (EC, 19%-28%), and thyroid cancer (TC, 6%-38%). Current risks are likely overestimated due to ascertainment bias. We aimed to provide more accurate and personalized cancer risks.This was a European, adult PHTS cohort study with data from medical files, registries, and/or questionnaires. Cancer risks and hazard ratios were assessed with Kaplan-Meier and Cox regression analyses, and standardized incidence ratios were calculated. Bias correction consisted of excluding cancer index cases and incident case analyses.A total of 455 patients were included, including 50.5% index cases, 372 with prospective follow-up (median 6 years, interquartile range = 3-10 years), and 159 of 281 females and 39 of 174 males with cancer. By age 60 years, PHTS-related cancer risk was higher in females (68.4% to 86.3%) than males (16.4% to 20.8%). Female BC risks ranged from 54.3% (95% confidence interval [CI] = 43.0% to 66.4%) to 75.8% (95% CI = 60.7% to 88.4%), with two- to threefold increased risks for PTEN truncating and approximately twofold for phosphatase domain variants. EC risks ranged from 6.4% (95% CI = 2.1% to 18.6%) to 22.1% (95% CI = 11.6% to 39.6%) and TC risks from 8.9% (95% CI = 5.1% to 15.3%) to 20.5% (95% CI = 11.3% to 35.4%). Colorectal cancer, renal cancer, and melanoma risks were each less than 10.0%.Females have a different BC risk depending on their PTEN germline variant. PHTS patients are predominantly at risk of BC (females), EC, and TC. This should be the main focus of surveillance. These lower, more unbiased and personalized risks provide guidance for optimized cancer risk management.
Tracing Bai-Yue Ancestry in Aboriginal Li People on Hainan Island
Authors: Hao Chen, Rong Lin, Yan Lu, Rui Zhang, Yang Gao, Yungang He, Shuhua Xu
Journal: Molecular Biology and Evolution (2022)

Abstract As the most prevalent aboriginal group on Hainan Island located between South China and the mainland of Southeast Asia, the Li people are believed to preserve some unique genetic information due to their isolated circumstances, although this has been largely uninvestigated. We performed the first whole-genome sequencing of 55 Hainan Li (HNL) individuals with high coverage (∼30–50×) to gain insight into their genetic history and potential adaptations. We identified the ancestry enriched in HNL (∼85%) is well preserved in present-day Tai-Kadai speakers residing in South China and North Vietnam, that is, Bai-Yue populations. A lack of admixture signature due to the geographical restriction exacerbated the bottleneck in the present-day HNL. The genetic divergence among Bai-Yue populations began ∼4,000–3,000 years ago when the proto-HNL underwent migration and the settling of Hainan Island. Finally, we identified signatures of positive selection in the HNL, some outstanding examples included FADS1 and FADS2 related to a diet rich in polyunsaturated fatty acids. In addition, we observed that malaria-driven selection had occurred in the HNL, with population-specific variants of malaria-related genes (e.g., CR1) present. Interestingly, HNL harbors a high prevalence of malaria leveraged gene variants related to hematopoietic function (e.g., CD3G) that may explain the high incidence of blood disorders such as B-cell lymphomas in the present-day HNL. The results have advanced our understanding of the genetic history of the Bai-Yue populations and have provided new insights into the adaptive scenarios of the Li people.
Improved Survival for Patients with Systemic Sclerosis–associated Pulmonary Arterial Hypertension: The Johns Hopkins Registry
Authors: Hussein J. Hassan, Mario Naranjo, Nour Ayoub, Traci Housten, Steven Hsu, Aparna Balasubramanian, Catherine E. Simpson, Rachel L. Damico, Stephen C. Mathai, Todd M. Kolb, Paul M. Hassoun
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

To date, it remains unclear whether recent changes in the management of patients with systemic sclerosis-associated pulmonary hypertension (SSc-PH) have improved survival.
Quantifying Clinical Utility of Adjuvant Abemaciclib in Patients With High-risk Early Breast Cancer Who Received Neoadjuvant Chemotherapy—Reply
Authors: Ran Jennifer Wei, Miguel Martin, Stephen R. D. Johnston
Journal: JAMA Oncology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Treatment With Stereotactic Ablative Radiotherapy for Up to 5 Oligometastases in Patients With Cancer
Authors: Robert Olson, Will Jiang, Mitchell Liu, Alanah Bergman, Devin Schellenberg, Benjamin Mou, Abraham Alexander, Hannah Carolan, Fred Hsu, Stacy Miller, Siavash Atrchian, Elisa Chan, Clement Ho, Islam Mohamed, Angela Lin, Tanya Berrang, Andrew Bang, Nick Chng, Quinn Matthews, Sarah Baker, Vicky Huang, Ante Mestrovic, Derek Hyde, Chad Lund, Howard Pai, Boris Valev, Shilo Lefresene, Scott Tyldesley
Journal: JAMA Oncology (2022)

After the publication of the landmark SABR-COMET trial, concerns arose regarding high-grade toxic effects of treatment with stereotactic ablative body radiotherapy (SABR) for oligometastases.To document toxic effects of treatment with SABR in a large cohort from a population-based, provincial cancer program.From November 2016 to July 2020, 381 patients across all 6 cancer centers in British Columbia were treated in this single-arm, phase 2 trial of treatment with SABR for patients with oligometastatic or oligoprogressive disease. During this period, patients were only eligible to receive treatment with SABR in these settings in trials within British Columbia; therefore, this analysis is population based, with resultant minimal selection bias compared with previously published SABR series.Stereotactic ablative body radiotherapy to up to 5 metastases.Rate of grade 2, 3, 4, and 5 toxic effects associated with SABR.Among 381 participants (122 women [32%]), the mean (SD; range) age was 68 (11.1; 30-97) years, and the median (range) follow-up was 25 (1-54) months. The most common histological findings were prostate cancer (123 [32%]), colorectal cancer (63 [17%]), breast cancer (42 [11%]), and lung cancer (33 [9%]). The number of SABR-treated sites were 1 (263 [69%]), 2 (82 [22%]), and 3 or more (36 [10%]). The most common sites of SABR were lung (188 [34%]), nonspine bone (136 [25%]), spine (85 [16%]), lymph nodes (78 [14%]), liver (29 [5%]), and adrenal (15 [3%]). Rates of grade 2, 3, 4, and 5 toxic effects associated with SABR (based on the highest-grade toxic effect per patient) were 14.2%; (95% CI, 10.7%-17.7%), 4.2% (95% CI, 2.2%-6.2%), 0%, and 0.3% (95% CI, 0%-0.8%), respectively. The cumulative incidence of grade 2 or higher toxic effects associated with SABR at year 2 by Kaplan-Meier analysis was 8%, and for grade 3 or higher, 4%.This single-arm, phase 2 clinical trial found that the incidence of grade 3 or higher SABR toxic effects in this population-based study was less than 5%. Furthermore, the rates of grade 2 or higher toxic effects (18.6%) were lower than previously published for SABR-COMET (29%). These results suggest that SABR treatment for oligometastases has acceptable rates of toxic effects and potentially support further enrollment in randomized phase 3 clinical trials.ClinicalTrials.gov Identifier: NCT02933242.
Identification of Deaths Caused by Cancer and COVID-19 in the US During March to December 2020
Authors: Xuesong Han, Xin Hu, Jingxuan Zhao, Ahmedin Jemal, K. Robin Yabroff
Journal: JAMA Oncology (2022)

This cross-sectional study uses 2020 mortality data in the US to analyze deaths caused by cancer and COVID-19 in terms of demographic characteristics, cancer site, and place of death.
Defining a Therapeutic Ratio for Stereotactic Ablative Radiation Therapy in Oligometastatic Disease—Another Piece of the Puzzle
Authors: Matthew S. Katz, Gregory A. Russo
Journal: JAMA Oncology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal